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October 13, 2015

Guest Post -- The Emergent Microbiome: A Revolution for the Life Sciences – Part III, Psychobiotics

This is the third article in a series on advancements in microbiome research and development. This installment reviews the area of microbiome research known as the "gut-brain-axis" and therapies related thereto, which have been dubbed "pyschobiotics." Upcoming articles will continue to review important topics in this technology area, and patents of interest.

By Jessica Miles* and Anthony D. Sabatelli** --

Research into the microbiome focuses heavily on bacteria living in the gut, which houses more bacteria than any other organ. These bacteria are being studied not only because they play a role in gastrointestinal disorzers like Inflammatory Bowel Disease (IBD), Crohn's Disease, and colorectal cancer, but also because they can influence diverse and distal organs. The gut-brain-axis -- the term for the neurochemical pathway between the intestine and the brain -- is a prominent example of such a relationship. As the research is starting to progress in this area, we are also beginning to see patents relating to this area.

The gut-brain-axis and "psychobiotics"

The gut-brain-axis begins with the enteric nervous system (ENS), a network of neurons that runs through the gastrointestinal tract. From there, the gut communicates with the brain via the vagus nerve, which connects the ENS to the central nervous system, transmitting signals up the spinal cord and to the brain. However, the link between bowel and brain is bidirectional, as the brain controls the immune system and other autonomic functions that shape the bacterial populations living in the gut.

The gut microbiota shapes brain function by promoting the synthesis of neurochemicals that directly interact with the ENS. The trillions of microbes living in the human intestine produce a multitude of chemicals, called metabolites. Some metabolites are the byproducts of bacterial fermentation of dietary fiber; one of these, butyrate, influences brain function by regulating neuronal gene expression. Others modulate critically important neuroendocrine molecules. For example, work published earlier this year demonstrates that specific gut microbiome members interact with intestinal cells to stimulate serotonin production, indicating that these bacteria play a principle role in regulating the body's reservoir of this important neurotransmitter and mood-regulator. Additional recent and emerging research implicates gut bacteria in the production of such well-known neurotransmitters as dopamine, gamma-Aminobutyric acid (GABA), histamine, noradrenaline, and adrenaline.

Underlining the connection between the brain and the gut, patients with neurological and psychiatric disorders such as depression, anxiety, autism, and childhood hyperactivity often present with gastrointestinal illness. Because of this connection, and the fact that the intestine is the main site of synthesis for many of these psychoactive compounds, beneficial bacteria with potential psychiatric and neurological effects are being called "psychobiotics."

Current State of R&D

A watershed moment for psychobiotics came in 2013, when researchers at UCLA provided some of the earliest evidence that gut bacteria can alter human brain function and mood. This work came after several papers reported that probiotic strains could reduce depression- and anxiety-like behaviors in mice. Since then, there has been interest in understanding the interplay between bacteria and mood disorders and how pyschobiotics might be used to improve brain development and lessen behavioral symptoms associated with conditions such as autism. Notably, one of the first patents relating to this area of research was issued earlier this year. U.S. Patent No. 8,927,242 (reviewed in detail in the previous installment) generally relates to a bacterial therapy for treatment of a subset of psychiatric disorders in children, called PANDAS. This patent was granted to NuBiome, a California-based company specializing in treatments for autoimmune disorders.

There are also several patents pending for psychobiotic-based treatments. Symbiotix cofounder Sarkis Mazmanian has filed for two patent applications in this area of research: one relates to the use of bacterial probiotics for the treatment of anxiety, autism, and autism spectrum disorder, while the other relates to other therapies, including fecal transplantation, to treat these disorders. Autism researcher Sydney Finegold has also filed two patent applications, both relating to the use of antimicrobials andprobiotics to treat behavorial disorders. Another application, US 20140301995, generally relates to manipulating bifidobacteria and clostridia in the gut to improve serotonin levels. US 20150152484 covers the characterization of Prevotella, Coprococcus, Prevotellaceae, or Veillonellaceae bacteria in ASD patients. US 20150259728, which was filed in March, describes a treatment of anxiety-like behavior and stress-induced inflammation in children. The treatment is a prebiotic: a non-digestible carbohydrate that stimulates growth of the gut microbiota.

Closing

The gut-brain-axis represents an exciting frontier for microbiome studies. Despite their infancy, psychobiotics hold great promise for difficult-to-treat mood and psychiatric disorders. Although current patent and commercialization activity in this research area is low, this activity will increase as research this field continues to grow.